Epiretinal Macrophage-like Cells on Optical Coherence Tomography: Potential Inflammatory Imaging Biomarker of Severity in Diabetic Retinopathy

Purpose: To investigate the clinical value of epiretinal macrophage-like cells (eMLC) in different stages of diabetic retinopathy (DR), including diabetic macular edema (DME). Methods: One hundred and seventy-six eyes of 176 patients, including 31 diabetes eyes without retinopathy (NDR), 24 with mild non-proliferative DR (NPDR), 37 with moderate NPDR, 32 with severe NPDR, and 52 with proliferative DR (PDR), were compared to 30 healthy controls. The optic nerve head and macular region were examined using en face optical coherence tomography (OCT) and OCT angiography. A previously described technique was employed to measure the eMLCs on the inner limiting membrane. Results: The optic nerve head (ONH) and macular eMLC densities increased with worsening DR stage and were higher in moderate, severe NPDR and PDR, especially in eyes with DME (all adjusted p<0.01). The ONH and macular eMLC densities in the DME groups were higher than those in their corresponding non-DME groups at the same DR stage (all p<0.05). The average macular thickness was correlated with macular eMLC density (standardized β=0.661, p<0.001) in patients with diabetes. The proportion of eyes with larger and plumper eMLCs increased with worsening DR and was higher in moderate, severe NPDR, PDR and eyes with DME (p=0.018, p<0.001, p<0.001 and p<0.001 respectively). Conclusions: Increased density along with morphological changes of eMLCs are observed beginning with moderate NPDR, and correlate with the progression of DR, including DME.